Project B12

Delineating distinctions in cellular and molecular functions between the interstitial matrix and the basement membrane during cardiac morphogenesis

Formation of the cardiac valves is critical for heart function and optimal blood circulation. Valve development requires the extracellular matrix (ECM) that provides physical scaffold for growth and differentiation. Notably, the functional distinctions of different ECM types, specifically the basement membrane versus the interstitial matrix, during cardiac morphogenesis are unknown. This is a critical gap as the two ECM types exhibit different biomechanical properties and signaling functions.

In our current project, using the zebrafish heart as a model, we will uncover the functions of core components of the basement membrane (laminins) and the interstitial matrix (fibrillar collagen types I and V) during valvulogenesis at single cell resolution. We focus on the dynamic interfaces of the basement membrane and the interstitial matrix with different valve cells – endothelial and fibroblast cells – that lead to optimal valve tissue shapes. We will elucidate the affected cellular processes upon disruption of basement membrane or interstitial matrix that can lead to dysfunctional valves. We will further investigate the feedback mechanisms between cardiac contraction- and blood flow-induced mechanical forces and ECM dynamics in the valve. We combine high-resolution confocal imaging, genetic and pharmaceutical manipulation of embryos and transcriptomic assays to address our questions.